Chemical Probe Technology and Applications in Chemical Proteomics

In life sciences research, the expression level of proteins is not equivalent to their functional state. While proteomics reveals the abundance changes of proteins under different conditions, it is difficult to accurately capture the 'active state' protein populations. Thus, chemical proteomics has emerged. Among them,Chemical Probes Technologyis a key support method in this field. By designing chemical probes with specific reactivity, researchers can selectively label and enrich active proteins in complex biological systems, enabling precise functional proteome analysis with mass spectrometry platforms.

 

Chemical probes typically consist of the following three core components:

1. Recognition Moiety: Recognizes and binds the active sites of proteins, often mimicking substrate structure or binding site residues.

2. Reactive Warhead: Covalently binds to target proteins, ensuring the stability of the labeling.

3. Reporter Tag: Used for subsequent enrichment or detection, such as biotin, fluorophores, radioactive labels, or click chemistry-compatible groups (such as alkynes).

Through the synergistic action of the above modules, chemical probes can achieve high-selectivity labeling of active enzymes or functional proteins, revealing dynamic functions without affecting endogenous expression profiles.

 

1. Activity-Based Probes (ABPs)

ABPs are the most widely used type of chemical probes, extensively applied in studies of serine hydrolases, cysteine proteases, protein tyrosine phosphatases, and other functional enzymes.Common probe types include: 

(1) Fluorophosphonate-based (Ser Hydrolase)

(2) Iodoacetamide, cyanoacrylamide-based (Cys Protease)

(3) Phenylphosphonate derivatives (Phosphatase)

 

2. Click Chemistry-Compatible Probes

These probes typically first label target proteins with a small molecule precursor, followed by connection to visualization or enrichment tags through click chemistry reactions (such as CuAAC).Suitable for experimental systems sensitive to probe interference. 

Advantages include:

(1) Reduced molecular weight, increased cell permeability

(2) Flexible introduction of different fluorescent/biotin tags

 

3. Photoaffinity Probes

Used to capture protein-small molecule interactions, usually containing photo-reactive groups (such as aryl azides, benzophenones), activated by UV irradiation to crosslink with proteins.

Suitable for:

(1) Discovery of small molecule drug targets

(2) Pharmacological mechanism analysis

 

1. Active Protein Profiling

Chemical probes allow researchers to label active proteins in situ, combined with mass spectrometry quantitative analysis to construct 'active protein maps' of cells or tissues, revealing truly functional nodes in regulatory networks.

 

2. Target Validation and Small Molecule Screening

Probe competition experiments can functionally verify the target binding ability of candidate small molecule drugs, providing data support for lead compound screening and optimization.

 

3. Dynamic Signal Pathway Monitoring

Under different stimuli or treatment conditions, chemical probes can track the trajectory of specific enzyme activity changes over time, aiding in the establishment of more realistic biological models.

 

Biotech Pack Biological Technology leverages its deep expertise in both proteomics and organic synthesis to establish a comprehensive chemical probe technology platform, covering:

• Probe design and synthesis: Rapid design of recognition-reaction-report modules based on target structure.

• High-throughput labeling and enrichment process: Based on Click Chemistry and automated bead enrichment.

• High-resolution mass spectrometry platform: Fully supported by Orbitrap Exploris, Fusion Lumos, and other equipment.

• Bioinformatics analysis: Quantitative active protein mining, pathway enrichment, competition index calculation, etc.

In addition, we support customers in the custom development of new probes under specific mechanisms, assisting projects from basic research to target validation and druggable evaluation stages.

 

As an important component of functional proteomics, chemical probe technology is providing higher resolution and more specific detection strategies for protein function research. Whether in mechanism analysis, disease biomarker discovery, or drug target screening, this technology shows significant application potential.If you are exploring target proteins, active mechanisms, or functional regulation, feel free to contactBiotech Pack Biological Technologyand we will empower your research projects with innovative probe strategies and professional analytical capabilities.

 

Biotech Pack Biological Technology—Characterization of Biological Products, High-quality Service Provider in Multi-omics Biological Mass Spectrometry Detection

 

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